| Autor | Cortopassi, Wilian Augusto | |
| Autor | Gunderson, Emma | |
| Autor | Annunciato, Yasmin | |
| Autor | Silva, Antony E S | |
| Autor | Ferreira, Amália Dos Santos | |
| Autor | Teles, Carolina Bioni Garcia | |
| Autor | Pimentel, Andre S | |
| Autor | Ramamoorthi, Roopa | |
| Autor | Gazarini, Marcos L | |
| Autor | Meneghetti, Mario R | |
| Autor | Guido, Rafael V C | |
| Autor | Pereira, Dhelio Batista | |
| Autor | Jacobson, Matthew P | |
| Autor | Krettli, Antoniana Ursine | |
| Autor | Aguiar, Anna Caroline Campos | |
| Data de acesso | 2023-02-03T18:17:34Z | |
| Data de disponibilização | 2023-02-03T18:17:34Z | |
| Data do publicação | 2022 | |
| Citação | Fighting Plasmodium chloroquine resistance with acetylenic chloroquine analogues. Int J Parasitol Drugs Drug Resist. 2022 Dec;20:121-128. doi: 10.1016/j.ijpddr.2022.10.003. | en_US |
| ISSN | 2211-3207 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/56866 | |
| Idioma | eng | en_US |
| Editor | Elsevier | en_US |
| Direito Autoral | restricted access | |
| Título | Fighting Plasmodium chloroquine resistance with acetylenic chloroquine analogues | en_US |
| Tipo do documento | Article | |
| Resumo em Inglês | Malaria is among the tropical diseases that cause the most deaths in Africa. Around 500,000 malaria deaths are reported yearly among African children under the age of five. Chloroquine (CQ) is a low-cost antimalarial used worldwide for the treatment of Plasmodium vivax malaria. Due to resistance mechanisms, CQ is no longer effective against most malaria cases caused by P. falciparum. The World Health Organization recommends artemisinin combination therapies for P. falciparum malaria, but resistance is emerging in Southeast Asia and some parts of Africa. Therefore, new medicines for treating malaria are urgently needed. Previously, our group identified the 4-aminoquinoline DAQ, a CQ analog containing an acetylenic bond in its side chain, which overcomes CQ resistance in K1 P. falciparum strains. In this work, the antiplasmodial profile, drug-like properties, and pharmacokinetics of DAQ were further investigated. DAQ showed no cross-resistance against standard CQ-resistant strains (e.g., Dd2, IPC 4912, RF12) nor against P. falciparum and P. vivax isolates from patients in the Brazilian Amazon. Using drug pressure assays, DAQ showed a low propensity to generate resistance. DAQ showed considerable solubility but low metabolic stability. The main metabolite was identified as a mono N-deethylated derivative (DAQM), which also showed significant inhibitory activity against CQ-resistant P. falciparum strains. Our findings indicated that the presence of a triple bond in CQ-analogues may represent a low-cost opportunity to overcome known mechanisms of resistance in the malaria parasite. | en_US |
| Afiliação | Department of Pharmaceutical Chemistry, University of California, San Francisco, USA. | en_US |
| Afiliação | Department of Pharmaceutical Chemistry, University of California, San Francisco, USA. | en_US |
| Afiliação | Department of Biosciences, Federal University of São Paulo, Santos, SP, Brazil. | en_US |
| Afiliação | Group of Catalysis and Chemical Reactivity Group, Institute of Chemistry and Biotechnology, Federal University of Alagoas, Maceió, AL, Brazil. | en_US |
| Afiliação | Oswaldo Cruz Foundation. Leishmaniasis and Malaria Bioassay Platform. Porto Velho. Rondônia, Brazil. | en_US |
| Afiliação | Oswaldo Cruz Foundation. Leishmaniasis and Malaria Bioassay Platform. Porto Velho. Rondônia, Brazil. | en_US |
| Afiliação | Department of Chemistry. Pontifical Catholic University of Rio de Janeiro. RJ, Brazil. | en_US |
| Afiliação | Catalyst Program. University of California. San Francisco, USA. | en_US |
| Afiliação | Department of Biosciences, Federal University of São Paulo, Santos, SP, Brazil. | en_US |
| Afiliação | Group of Catalysis and Chemical Reactivity Group. Institute of Chemistry and Biotechnology. Federal University of Alagoas. Maceió, AL, Brazil. | en_US |
| Afiliação | São Carlos Institute of Physics. University of Sao Paulo. São Carlos, SP, Brazil. | en_US |
| Afiliação | Research Center in Tropical Medicine of Rondônia. Porto Velho, RO, Brazil. | en_US |
| Afiliação | Department of Pharmaceutical Chemistry. University of California. San Francisco, USA. | en_US |
| Afiliação | Malaria Laboratory. René Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil. | en_US |
| Afiliação | Department of Biosciences. Federal University of São Paulo. Santos, SP, Brazil/São Carlos Institute of Physics. University of Sao Paulo. São Carlos, SP, Brazil. | en_US |
| Palavras-chave em inglês | ACTs | en_US |
| Palavras-chave em inglês | Chloroquine | en_US |
| Palavras-chave em inglês | DAQ | en_US |
| Palavras-chave em inglês | Malaria | en_US |
| Palavras-chave em inglês | Resistance | en_US |
| Data de embargo | 2090-12-31 | |
